Nitrogen and Hindered Phenol Containing Dual Functional Macromolecular Antioxidants: Synthesis, Performances and Applications

ABSTRACT

Disclosed are compounds represented by structural formula (I): 
     
       
         
         
             
             
         
       
     
     methods of producing compounds represented by structural formula (I). and their use in inhibiting oxidation in an oxidizable material.

RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.12/854,347, filed Aug. 11, 2010, which is a divisional of U.S.application Ser. No. 11/360,020, filed Feb. 22, 2006, which claims thebenefit of U.S. Provisional Application No. 60/655,169, filed on Feb.22, 2005. The entire teachings of the above applications areincorporated herein by reference.

BACKGROUND OF THE INVENTION

Antioxidants are employed to prevent oxidation in a wide range ofmaterials, for example, plastics, elastomers, lubricants, petroleumbased products (lubricants, gasoline, aviation fuels, and engine oils),cooking oil, cosmetics, processed food products, and the like. Whilemany antioxidants exist, there is a continuing need for new antioxidantsthat have improved properties.

SUMMARY OF THE INVENTION

The present invention relates to compounds containing dualfunctionalities of aromatic amines and hindered phenols that can beuseful as stabilizers for organic materials, lubricants and petroleumbased products, plastics and elastomers, cosmetics, foods and cookingoils, and other materials. In particular, the present invention pertainsto highly effective antioxidant macromolecules described herein. Thisinvention also reports an improved, highly efficient and economicalprocess for the synthesis of amine (nitrogen) and sterically hinderedphenol containing dual functional macromolecules. The design ofmacromolecules in this invention can incorporate at least twoantioxidant moieties having different reactivities. The presentinvention also discloses their superior antioxidant performance comparedto presently used commercial antioxidants. This is demonstratedespecially in both synthetic and petroleum base stocks (Group I, II andIII). In general one unique feature and design of the antioxidantsdescribed herein is their improved solubility in many commerciallyavailable oils and lubricants compared with currently availableantioxidants.

In one embodiment the present invention is a compound represented bystructural formula (I):

Each R_(a) is independently an optionally substituted alkyl. Each R_(b)is independently an optionally substituted alkyl. Each R_(c) isindependently an optionally substituted alkyl or an optionallysubstituted alkoxycarbonyl. R_(x) is —H or an optionally substitutedalkyl. R_(y) is —H or an optionally substituted alkyl. Each R′ isindependently —H or an optionally substituted alkyl. R″ is —H, anoptionally substituted alkyl, an optionally substituted aryl or anoptionally substituted aralkyl. n is an integer from 1 to 10. m is aninteger from 1 to 10. s is an integer from 0 to 5. t is an integer from0 to 4. u is an integer from 1 to 4. With the proviso that when n is 1,then either ring C is not:

s is not 0, or R″ is not —H.

In another embodiment, the present invention is a method of producing acompound represented structural formula (I). The method comprisescombining a phenol derivative, an amine and an aldehyde in the presenceof a solvent, wherein the phenol derivative comprises at least oneunsubstituted ring-carbon atom. Followed by refluxing the combination toproduce the compound, and finally isolating the compound.

In yet another embodiment, the present invention is a method ofproducing a compound represented structural formula (I). The methodcomprises combining a amino-phenol derivative with an amine in thepresence of a solvent. Followed by refluxing the combination to producethe compound, and finally isolating the compound.

In yet another embodiment, the present invention is a method ofproducing a compound represented structural formula (I). The methodcomprises combining a phenolic-carbonyl derivative represented by thefollowing structural formula:

with an amine in the presence of a solvent. Followed by refluxing thecombination to produce a schiff's base, reducing the schiff's base witha reducing agent to produce the compound, and finally isolating thecompound.

In another embodiment, the present invention is a method of producing acompound represented structural formula (I). The method comprisescombining a formaldehyde-sodium bisulfite adduct with an amine toproduce a methylsulfonate sodium salt in an aqueous media. Followed bythe nucleophilic displacement of the sulfonate group with a sodium orpotassium salt of a phenol derivative, in an aqueous media wherein thenucleophilic displacement is catalyzed by base, to produce the compound,and finally isolating the compound.

In another embodiment the present invention is a method of preventingoxidation in an oxidizable material, comprising combining the oxidizablematerial with a compound of the present invention.

The antioxidants described herein which are prepared by the disclosedprocesses in general are superior antioxidants (compared to currentlyavailable antioxidants) against oxidative, thermal degradation oforganic materials. These macromolecular antioxidants generally havecomparatively higher antioxidant activities along with improved thermalstability and performance in a wide range of materials including but notlimited to plastics, elastomers, lubricants, petroleum based products(lubricants, gasoline, aviation fuels, and engine oils), cooking oil,cosmetics, processed food products.

The processes of the present invention have many advantages which canallow improved synthesis of these macromolecular antioxidants. Forexample, the disclosed processes can be economically carried out in themelt phase without the presence of catalysts. Moreover, the processesdescribed herein generally reduce or eliminate purification steps forthe final product compared to existing syntheses, which can lead to asuperior performance/cost ratio for the product and reduced amounts ofwaste.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIG. 1, is a graph of Oxidative Induction Time (OIT) values ofStructural Formula A of the invention versus Commercial antioxidants(AO's) in Group II Lubricating Oils.

FIG. 2, is a graph of the performance comparison of Oxidative InductionTime (OIT) values of commercial antioxidants versus antioxidants of thepresent invention in GII base oil at 200 ppm by differential scanningcalorimetry (DSC).

FIG. 3, is a graph of commercial Irganox 1010 versus antioxidants of thepresent invention in polypropylene at 1000 ppm by DSC.

DETAILED DESCRIPTION OF THE INVENTION

A description of preferred embodiments of the invention follows.

As used herein, “dual functional” means any molecule with two functionalgroups which can optionally be the same or in certain embodiment aredifferent, such as amine and hydroxy.

As used herein “adduct” means chemically linked

Sterically hindered, as used herein means that the substituent group(e.g., bulky alkyl group) on a ring carbon atom adjacent (or para) to aring carbon atom substituted with a phenolic hydroxy group (or thiol oramine group), is large enough to sterically hinder the phenolic hydroxygroup (or thiol or amine groups). This steric hindrance, in certainembodiments results in more labile or weak bonding between the oxygenand the hydrogen (or sulfur or nitrogen and hydrogen) and in turnenhances the stability and antioxidant activity (proton donatingactivity) of the sterically hindered antioxidant.

Repeat units of the antioxidants of the invention include substitutedbenzene molecules. Some of these benzene molecules are typically basedon phenol or a phenol derivative, such that they have at least onehydroxyl or ether functional group. In certain embodiments, the benzenemolecules have a hydroxyl group. The hydroxyl group can be a freehydroxyl group and can be protected or have a cleavable group attachedto it (e.g., an ester group). Such cleavable groups can be releasedunder certain conditions (e.g., changes in pH), with a desired shelflife or with a time-controlled release (e.g., measured by thehalf-life), which allows one to control where and/or when an antioxidantcan exert its antioxidant effect. The repeat units can also includeanalogous thiophenol and aniline derivatives, e.g., where the phenol —OHcan be replaced by —SH, —NH—, and the like.

Substituted benzene repeat units of an antioxidant of the invention arealso typically substituted with a bulky alkyl group or ann-alkoxycarbonyl group. In certain embodiments, the benzene monomers aresubstituted with a bulky alkyl group. In certain other embodiments, thebulky alkyl group is located ortho or meta to a hydroxyl group on thebenzene ring, typically ortho. A “bulky alkyl group” is defined hereinas an alkyl group that is branched alpha- or beta- to the benzene ring.In certain other embodiments, the alkyl group is branched alpha to thebenzene ring. In certain other embodiments, the alkyl group is branchedtwice alpha to the benzene ring, such as in a tert-butyl group. Otherexamples of bulky alkyl groups include isopropyl, 2-butyl, 3-pentyl,1,1-dimethylpropyl, 1-ethyl-1-methylpropyl and 1,1-diethylpropyl. Incertain other embodiments, the bulky alkyl groups are unsubstituted, butthey can be substituted with a functional group that does not interferewith the antioxidant activity of the molecule. Straight chainedalkoxylcarbonyl groups include methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, n-butoxycarbonyl and n-pentoxycarbonyl.N-propoxycarbonyl is a preferred group. Similar to the bulky alkylgroups, n-alkoxycarbonyl groups are optionally substituted with afunctional group that does not interfere with the antioxidant activityof the molecule.

In one embodiment the present invention is a compound represented bystructural formula (I) wherein the variables are as described asfollows:

Each R_(a) is independently an optionally substituted alkyl. In oneembodiment, each R_(a) is independently a C1-C20 alkyl. In anotherembodiment, each R_(a) is independently a C1-C10 alkyl. In anotherembodiment, each R_(a) is independently selected from the groupconsisting of:

In another embodiment R_(a) is:

Each R_(b) is independently an optionally substituted alkyl.

Each R_(c) is independently an optionally substituted alkyl or anoptionally substituted alkoxycarbonyl. In one embodiment, each R_(c) isindependently a C1-C10 alkyl.

R_(x) is —H or an optionally substituted alkyl. R_(y) is —H or anoptionally substituted alkyl. In one embodiment, R_(x) and R_(y) are —H.

Each R′ is independently —H or an optionally substituted alkyl. In oneembodiment, one R′ is —H. In another embodiment, both R′ are —H.

R″ is —H, an optionally substituted alkyl, an optionally substitutedaryl or an optionally substituted aralkyl. In one embodiment, R″ is —H,a C1-C20 alkyl or an optionally substituted aralkyl. In anotherembodiment, R″ is —H, a C1-C10 alkyl or a substituted benzyl group. Inyet another embodiment, R″ is —H. In yet another embodiment, R″ is:

In yet another embodiment R″ is selected from the group consisting of:

In yet another embodiment R″ is:

n is an integer from 1 to 10. In one embodiment, n is an integer from 1to 6. In another embodiment, n is 1. In yet another embodiment, n is 2.In yet another embodiment, n is 3. In yet another embodiment, n is 4.

m is an integer from 1 to 10. In one embodiment, m is 1 or 2. In anotherembodiment, m is 1.

s is an integer from 0 to 5. In one embodiment, s is 0 or 1. In anotherembodiment, s is 0.

t is an integer from 0 to 4. In one embodiment, t is 0.

u is an integer from 1 to 4. In one embodiment, u is 1 or 2.

In certain embodiments for compounds of the present invention, includingthose represented by structural formula (I), when n is 1, the eitherring C is not:

s is not 0, or R″ is not —H.

In one embodiment of the present invention for the compounds representedby structural formula (I):

Each R_(a) is independently a C1-C20 alkyl. Each R_(c) is independentlya C1-C10 alkyl. R″ is —H, a C1-C20 alkyl or an optionally substitutedaralkyl, and the remainder of the variables are as described above forstructural formula (I).

In another embodiment of the present invention for compounds representedby structural formula (I): one R′ is —H, t is O, R_(x) and R_(y) are —Hand the compounds are represented by structural formula (II):

-   -   (II)        and the remainder of the variables are as described in the        immediately preceding paragraph or for structural formula (I).

In another embodiment of the present invention for the compoundsrepresented by structural formula (II):

m is 1 or 2.

s 0 or 1.

u is 1 or 2, and the remainder of the variables are as described in theimmediately preceding paragraph or for structural formula (I).

In another embodiment of the present invention for compounds representedby structural formula (II): both R′ are —H and m is 1 and the compoundsare represented by structural formula (III):

and the remainder of the variables are as described in the immediatelypreceding paragraph or for structural formula (I) or (II).

In another embodiment of the present invention for the compoundsrepresented by structural formula (III):

Each R_(a) is independently a C1-C10 alkyl.

R″ is —H, a C1-C10 alkyl or a substituted benzyl group.

n is an integer from 1 to 6, and the remainder of the variables are asdescribed in the immediately preceding paragraph or for structuralformula (I) or (II).

In another embodiment of the present invention for compounds representedby structural formula (III): n is 1, s is 0 and R″ is —H and thecompounds are represented by structural formula (IV):

with the proviso that ring C is not:

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In certain embodiments of the present invention the compoundsrepresented by structural formula (III) or (IV) are represented by thefollowing structural formulas:

In another embodiment of the present invention for compounds representedby structural formula (III): n is 1 and the compounds are represented bystructural formula (V):

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In another embodiment of the present invention for compounds representedby structural formula (III): s is 0 and the compounds are represented bystructural formula (VI):

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In another embodiment of the present invention for compounds representedby structural formula (III): R″ is —H and the compounds are representedby structural formula (VII):

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In certain embodiments of the present invention the compoundsrepresented by structural formula (III), (V), (VI) or (VII) arerepresented by the following structural formulas:

In another embodiment of the present invention for compounds representedby structural formula (III): R″ is —H and n is 1 and the compounds arerepresented by structural formula (VIII):

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In certain embodiments of the present invention the compoundsrepresented by structural formula (III) or (VIII) are represented by thefollowing structural formulas:

In another embodiment of the present invention for compounds representedby structural formula (III): s is 0 and R″ is —H and the compounds arerepresented by structural formula (IX):

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In certain embodiments of the present invention the compoundsrepresented by structural formula (III) or (IX) are represented by thefollowing structural formulas:

In another embodiment of the present invention for compounds representedby structural formula (III): s is 0 and n is 0 and the compounds arerepresented by structural formula (X):

and the remainder of the variables are as described above for structuralformula (I), (II) or (III).

In certain embodiments of the present invention the compoundsrepresented by structural formula (III) or (X) are represented by thefollowing structural formulas:

In another embodiment of the present invention the compound isrepresented by:

The term “alkyl” as used herein means a saturated straight-chain,branched or cyclic hydrocarbon. When straight-chained or branched, analkyl group is typically C1-C20, more typically C1-C10; when cyclic, analkyl group is typically C3-C12, more typically C3-C7. Examples of alkylgroups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyland tert-butyl and 1,1-dimethylhexyl.

The term “alkoxy” as used herein is represented by —OR**, wherein R** isan alkyl group as defined above.

The term “carbonyl” as used herein is represented by —C(═O)R**, whereinR** is an alkyl group as defined above.

The term “alkoxycarbonyl” as used herein is represented by —C(═O)OR**,wherein R** is an alkyl group as defined above.

The term “aromatic group” includes carbocyclic aromatic rings andheteroaryl rings. The term “aromatic group” may be used interchangeablywith the terms “aryl”, “aryl ring” “aromatic ring”, “aryl group” and“aromatic group”.

Carbocyclic aromatic ring groups have only carbon ring atoms (typicallysix to fourteen) and include monocyclic aromatic rings such as phenyland fused polycyclic aromatic ring systems in which a carbocyclicaromatic ring is fused to one or more aromatic rings (carbocyclicaromatic or heteroaromatic). Examples include 1-naphthyl, 2-naphthyl,1-anthracyl and 2-anthracyl. Also included within the scope of the term“carbocyclic aromatic ring”, as it is used herein, is a group in whichan aromatic ring is fused to one or more non-aromatic rings (carbocyclicor heterocyclic), such as in an indanyl, phthalimidyl, naphthimidyl,phenanthridinyl, or tetrahydronaphthyl.

The term “heteroaryl”, “heteroaromatic”, “heteroaryl ring”, “heteroarylgroup” and “heteroaromatic group”, used alone or as part of a largermoiety as in “heteroaralkyl” refers to heteroaromatic ring groups havingfive to fourteen members, including monocyclic heteroaromatic rings andpolycyclic aromatic rings in which a monocyclic aromatic ring is fusedto one or more other aromatic ring (carbocyclic or heterocyclic).Heteroaryl groups have one or more ring heteroatoms. Examples ofheteroaryl groups include 2-furanyl, 3-furanyl, N-imidazolyl,2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl,5-isoxazolyl, oxadiazolyl, oxadiazolyl, 2-oxazolyl, 4-oxazolyl,5-oxazolyl, N-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl,N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, triazolyl,tetrazolyl, 2-thienyl, 3-thienyl, carbazolyl, benzothienyl,benzofuranyl, indolyl, quinolinyl, benzothiazole, benzooxazole,benzimidazolyl, isoquinolinyl and isoindolyl. Also included within thescope of the term “heteroaryl”, as it is used herein, is a group inwhich an aromatic ring is fused to one or more non-aromatic rings(carbocyclic or heterocyclic).

The term non-aromatic heterocyclic group used alone or as part of alarger moiety refers to non-aromatic heterocyclic ring groups havingthree to fourteen members, including monocyclic heterocyclic rings andpolycyclic rings in which a monocyclic ring is fused to one or moreother non-aromatic carbocyclic or heterocyclic ring or aromatic ring(carbocyclic or heterocyclic). Heterocyclic groups have one or more ringheteroatoms, and can be saturated or contain one or more units ofunsaturation. Examples of heterocyclic groups include piperidinyl,piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl,tetrahydroquinolinyl, indolinyl, isoindolinyl, tetrahydrofuranyl,oxazolidinyl, thiazolidinyl, dioxolanyl, dithiolanyl, tetrahydropyranyl,dihydropyranyl, azepanyl and azetidinyl

The term “heteroatom” means nitrogen, oxygen, or sulfur and includes anyoxidized form of nitrogen and sulfur, and the quaternized form of anybasic nitrogen. Also the term “nitrogen” includes a substitutablenitrogen of a heteroaryl or non-aromatic heterocyclic group. As anexample, in a saturated or partially unsaturated ring having 0-3heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen maybe N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR″ (asin N-substituted pyrrolidinyl), wherein R″ is a suitable substituent forthe nitrogen atom in the ring of a non-aromatic nitrogen-containingheterocyclic group, as defined below. Preferably the nitrogen isunsubstituted.

As used herein the term non-aromatic carbocyclic ring as used alone oras part of a larger moiety refers to a non-aromatic carbon containingring which can be saturated or contain one or more units ofunsaturation, having three to fourteen atoms including monocyclic andpolycyclic rings in which the carbocyclic ring can be fused to one ormore non-aromatic carbocyclic or heterocyclic rings or one or morearomatic (carbocyclic or heterocyclic) rings

An optionally substituted aryl group as defined herein may contain oneor more substitutable ring atoms, such as carbon or nitrogen ring atoms.Examples of suitable substituents on a substitutable ring carbon atom ofan aryl group include halogen (e.g., —Br, Cl, I and F), —OH, C1-C4alkyl, C1-C4 haloalkyl, —NO₂, C1-C4 alkoxy, C1-C4 haloalkoxy, —CN, —NH₂,C1-C4 alkylamino, C1-C4 dialkylamino, —C(O)NH₂, —C(O)NH(C1-C4 alkyl),—C(O)(C1-C4 alkyl), —OC(O)(C1-C4 alkyl), —OC(O)(aryl),—OC(O)(substituted aryl), —OC(O)(aralkyl), —OC(O)(substituted aralkyl),—NHC(O)H, —NHC(O)(C1-C4 alkyl), —C(O)N(C1-C4 alkyl)₂, —NHC(O)O—(C1-C4alkyl), —C(O)OH, —C(O)O—(C1-C4 alkyl), —NHC(O)NH₂, —NHC(O)NH(C1-C4alkyl), —NHC(O)N(C1-C4 alkyl)₂, —NH—C(═NH)NH₂,—SO₂NH₂—SO₂NH(C1-C3alkyl), —SO₂N(C1-C3alkyl)₂, NHSO₂H, NHSO₂(C1-C4alkyl) and optionally substituted aryl. Preferred substituents on arylgroups are as defined throughout the specification. In certainembodiments aryl groups are unsubstituted.

Examples of suitable substituents on a substitutable ring nitrogen atomof an aryl group include C1-C4 alkyl, NH₂, C1-C4 alkylamino, C1-C4dialkylamino, —C(O)NH₂, —C(O)NH(C1-C4 alkyl), —C(O)(C1-C4 alkyl),—CO₂R**, —C(O)C(O)R**, —C(O)CH₃, —C(O)OH, —C(O)O—(C1-C4 alkyl),—SO₂NH₂—SO₂NH(C1-C3alkyl), —SO₂N(C1-C3alkyl)₂, NHSO₂H, NHSO₂(C1-C4alkyl), —C(═S)NH₂, —C(═S)NH(C1-C4 alkyl), —C(═S)N(C1-C4 alkyl)₂,—C(═NH)—N(H)₂, —C(═NH)—NH(C1-C4 alkyl) and —C(═NH)—N(C1-C4 alkyl)₂,

An optionally substituted alkyl group or non-aromatic carbocyclic orheterocyclic group as defined herein may contain one or moresubstituents. Examples of suitable substituents for an alkyl groupinclude those listed above for a substitutable carbon of an aryl and thefollowing: ═O, ═S, ═NNHR**, ═NN(R**)₂, ═NNHC(O)R**, ═NNHCO₂ (alkyl),═NNHSO₂ (alkyl), ═NR**, Spiro cycloalkyl group or fused cycloalkylgroup. R** in each occurrence, independently is —H or C1-C6 alkyl.Preferred substituents on alkyl groups are as defined throughout thespecification. In certain embodiments optionally substituted alkylgroups are unsubstituted.

A “spiro cycloalkyl” group is a cycloalkyl group which shares one ringcarbon atom with a carbon atom in an alkylene group or alkyl group,wherein the carbon atom being shared in the alkyl group is not aterminal carbon atom.

In yet another embodiment, the present invention is a method ofproducing a compound described herein. The method comprises the steps ofcombining a phenol derivative, an amine and an aldehyde in the presenceof a solvent, wherein the phenol derivative comprises at least oneunsubstituted ring-carbon atom. Refluxing the combination of the phenolderivative, amine and aldehyde to produce the compound, and isolatingthe compound.

In certain embodiments of the present invention, the phenol derivativeis represented by the following structural formula:

Each R_(c) is independently an optionally substituted alkyl oroptionally substituted alkoxycarbonyl. R′ is —H or an optionallysubstituted alkyl. u is an integer from 1 to 4. Additional values forthese variables are as described above. In one embodiment the phenolderivative is selected from:

In another embodiment, the amine is represented by the followingstructural formula:

Each R_(a) is independently an optionally substituted alkyl. Each R_(b)is independently an optionally substituted alkyl. Each R′ isindependently —H or an optionally substituted alkyl. n is an integerfrom 1 to 10. s is an integer from 0 to 5. t is an integer from 0 to 4.Additional values for these variables are as described above.

In certain embodiments the aldehyde used in the methods of the presentinvention is selected from the group consisting of paraformaldehyde,formaldehyde, butaldehyde and nonaldehyde.

In certain embodiments the solvent used in the methods of the presentinvention is selected from the group consisting of methanol, butanol,ethanol and toluene.

In certain embodiments of the present invention after combining theamine, aldehyde and phenol derivative in a suitable solvent thecombination is refluxed for between 1 and 48 hours, between 6 and 32hours or between 12 and 24 hours with optional stirring. In certainembodiments the combination is refluxed at a temperature between 20 and250° C., between 60 and 180° C. or between 100 and 120° C.

In certain embodiments of the present invention equimolar amounts of thephenol derivative and the amine are combined. In certain embodiments ofthe present invention the phenol derivative and the amine are combinedan a 1:0.5, 1:1.2, 1:1.5, 1:1.0 molar ratio of phenol derivative:amine.

The following schemes illustrate particular embodiments of this method:

R_(o) is H, optionally substituted alkyl, or optionally substitutedalkoxycarbonyl, all of the remainder of the variables are as describedabove.

R_(o) is H, optionally substituted alkyl, or optionally substitutedalkoxycarbonyl, all of the remainder of the variables are as describedabove.

R_(o) is H, optionally substituted alkyl, or optionally substitutedalkoxycarbonyl, all of the remainder of the variables are as describedabove.

R_(o) is H, optionally substituted alkyl, or optionally substitutedalkoxycarbonyl, all of the remainder of the variables are as describedabove.

In one embodiment of the present invention the following schemesillustrate the methods described above:

The variables R and R₁₋₈ described herein correspond to the variablesdescribed above for structural formulas (I) through (X) as follows R₁₋₄are equivalent to R_(b), R₅₋₈ are equivalent to R_(c), R is equivalentto R_(a), and n and m are the same.

In yet another embodiment the present invention is a method of producinga compound described herein. The method comprises the steps of combiningan amino-phenol derivative with an amine in the presence of a solvent.Refluxing the combination to produce the compound, and isolating thecompound.

In certain embodiments of the present invention the amino-phenolderivative is represented by the following structural formula:

Each R_(c) is independently an optionally substituted alkyl or anoptionally substituted alkoxycarbonyl. R′ is —H or an optionallysubstituted alkyl. R** is an optionally substituted alkyl. o is aninteger from 1 to 10. u is an integer from 1 to 4. Additional values forthese variables are as described above. In another embodiment theamino-phenol is selected from the group consisting of:

In another embodiment, the amine is represented by the followingstructural formula:

Each R_(a) is independently an optionally substituted alkyl. Each R_(b)is independently an optionally substituted alkyl. Each R′ isindependently —H or an optionally substituted alkyl. In certainembodiments one R′ is —H—H and the second R′ is —H or an optionallysubstituted alkyl. n is an integer from 1 to 10. s is an integer from 0to 5. t is an integer from 0 to 4. Additional values for these variablesare as described above.

In certain embodiments, in the methods of the present invention thesolvent is selected from the group consisting of toluene, methanol,ethanol and butanol.

In certain other embodiments of the present invention after combiningthe amine and amino-phenol derivative in a suitable solvent thecombination is refluxed at a temperature between 50 and 180° C., between90 and 130° C., between 100 and 110° C. In certain embodiments, thecombination is refluxed for between 1 and 48 hours, between 6 and 36hours, between 12 and 24 hours or between 18 and 20 hours.

In certain embodiments of the present invention equimolar amounts of theamino-phenol derivative and the amine are combined. In certainembodiments of the present invention the amino-phenol derivative and theamine are combined an a 1:0.5, 1:1.2, 1:1.5, 1:1.0 molar ratio ofamino-phenol derivative:amine

In one embodiment the above method can be conducted in one step and canbe conducted without catalyst. The process can be conducted by mixingtwo starting components in a suitable solvent and heating the reactionmixture to reflux as shown in Scheme E:

The variables are as described above.

In one embodiment, the above method involves mixing of stericallyhindered phenolic acid derivatives, preferably2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol with substituted aminese.g., N-phenyl-1,4-phenylene-diamine in a suitable solvent. The solventcan be a single solvent or mixture of two solvents. In anotherembodiment, the solvent is toluene.

One embodiment of the present invention is directed to combiningequimolar amounts of the starting components, e.g.,2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol andN-phenyl-1,4-phenylene-diamine, in toluene and refluxing the reactionmixture at, e.g., 100° C.

In certain embodiment the methods of the present invention are simple,efficient, economical and can be conducted without catalyst.

In certain other embodiments in the methods of the present invention,when solvent is used it can be recycled by separating the solvents fromthe reaction mixture using distillation.

In one embodiment, the present invention relates to a process orprocesses for the preparation of macromolecule antioxidants representedby Structural Formula I:

The disclosed synthesis of macromolecules (I) can be conducted in onestep and can be conducted without catalyst. The process can be conductedby mixing two starting components in a suitable solvent and heating thereaction mixture to reflux as shown in Scheme 1.

The disclosed process can involve mixing of sterically hindered phenolicacid derivatives, preferably2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol (III) with substitutedamines e.g., N-phenyl-1,4-phenylene-diamine (II) in a suitable solvent.The solvent can be a single solvent or mixture of two solvents. Thepreferred solvent for the process can be toluene. The preferred methodcan be mixing of equimolar amounts of the starting components, e.g.,2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol andN-phenyl-1,4-phenylene-diamine, in toluene and refluxing the reactionmixture at, e.g., 100° C. The disclosed process can be simple,efficient, economical and can be conducted without catalyst. Further,when solvent is used in the process, it can be recycled by separatingthe solvents from the reaction mixture using distillation Moreover, theabove mentioned reaction can also be performed under solvent-lessconditions, at 100-180° C., preferably at 110° C.

In yet another embodiment the present invention is a method of producinga compound described herein. The method comprises the steps of combininga phenolic-carbonyl derivative represented by the following structuralformula:

with an amine in the presence of a solvent. Refluxing the combination ofphenolic-carbonyl and amine to produce a schiff's base. Reducing theschiff's base with a reducing agent to produce the compound, andisolating the compound. o is an integer from 0 to 10. R* is —H or anoptionally substituted alkyl. Additional values for the variables are asdescribed above. In certain embodiments the phenolic carbonyl isselected from the group comprising:

In another embodiment, the amine is represented by the followingstructural formula:

Each R_(a) is independently an optionally substituted alkyl. Each R_(b)is independently an optionally substituted alkyl. Each R′ isindependently —H or an optionally substituted alkyl. n is an integerfrom 1 to 10. s is an integer from 0 to 5. t is an integer from 0 to 4.Additional values for these variables are as described above.

In certain embodiments of the present invention the solvent is selectedfrom the group consisting of toluene, methanol, ethanol and butanol.

In certain other embodiments of the present invention after combiningthe amine and phenolic-carbonyl derivative in a suitable solvent thecombination is refluxed at a temperature between 50 and 180° C., between60 and 130° C., between 70 and 110° C. In certain embodiments, thecombination is refluxed for between 1 and 48 hours, between 6 and 36hours, between 12 and 24 hours or between 18 and 20 hours.

In certain embodiments of the present invention equimolar amounts of thephenol-carbonyl derivative and the amine are combined. In certainembodiments of the present invention the amino-phenol derivative and theamine are combined an a 1:0.5, 1:1.2, 1:1.5, 1:1.0 molar ratio ofphenol-carbonyl derivative:amine

In certain embodiment the reducing agent is selected from the groupsconsisting of sodium borohydride, sodium cyanoborohydride and lithiumaluminum hydride. In certain other embodiments reduction takes place viacatalytic hydrogenation. In certain embodiments the catalytichydrogenation agents are Pd—C or Raney Ni.

In yet another embodiment the present invention is a method of producinga compound described herein. The method comprises the steps of combininga formaldehyde-sodium bisulfite adduct with an amine to produce amethylsulfonate sodium salt in an aqueous media. Followed by thenucleophilic displacement of the sulfonate group with sodium orpotassium salt of a phenol derivative, in an aqueous media, to producethe compound, and finally isolating the compound. In certain embodimentsthe nucleophilic displacement is promoted by base or catalyzed base. Incertain embodiments, both combination steps are carried out in anaqueous media.

In certain embodiments the formaldehyde-sodium bisulfite adduct isHO—CH₂—SO₃Na.

In certain embodiments the methylsulfonate sodium salt is4-(phenylamino)phenylamino methylsulfonate sodium salt.

In certain embodiments, the phenol derivative and amine are as describedabove.

In certain embodiments, the aqueous media is water.

In certain embodiments, the base is sodium hydroxide or potassiumhydroxide.

In one embodiments of the present invention, the compound is not:

The compounds of the present invention can be used as antioxidants toinhibit oxidation of an oxidizable material. Such as, for example toincrease the shelf life of an oxidizable material.

The antioxidant compounds of the present invention can be employed toinhibit the oxidation of an oxidizable material, for example bycontacting the material with an antioxidant compound made by the methodsof the present invention.

For purposes of the present invention, a method of “inhibitingoxidation” is a method that inhibits the propagation of a freeradical-mediated process. Free radicals can be generated by heat, light,ionizing radiation, metal ions and some proteins and enzymes. Inhibitingoxidation also includes inhibiting reactions caused by the presence ofoxygen, ozone or another compound capable of generating these gases orreactive equivalents of these gases.

As used herein the term “oxidizable material” is any material which issubject to oxidation by free-radicals or oxidative reaction caused bythe presence of oxygen, ozone or another compound capable of generatingthese gases or reactive equivalents thereof. In particular theoxidizable material is a lubricant or a mixture of lubricants.

The shelf life of many materials and substances contained within thematerials, such as packaging materials, are enhanced by the presence ofthe antioxidants of the present invention. The addition of anantioxidant of the present invention to a packaging material is believedto provide additional protection to the product contained inside thepackage. In addition, the properties of many packaging materialsthemselves, particularly polymers, are enhanced by the presence of anantioxidant regardless of the application (i.e., not limited to use inpackaging). Common examples of packaging materials include paper,cardboard and various plastics and polymers. A packaging material can becoated with an antioxidant (e.g., by spraying the antioxidant or byapplying as a thin film coating), blended with or mixed with anantioxidant, or otherwise have an antioxidant present within it. In oneexample, a thermoplastic such as polyethylene, polypropylene orpolystyrene can be melted in the presence of an antioxidant in order tominimize its degradation during the polymer processing.

The lifetime of lubricants, lubricant oils, mixtures thereof andcompositions comprising lubricants and lubricant oils in general can beimproved by contacting the lubricant, lubricant oil, mixtures thereof orcomposition comprising the lubricant or lubricant oil or mixturesthereof with compounds of the present invention, as described herein.

As used here, the terms “lubricants” and “lubricant oils” can be usedinterchangeably. Examples of lubricants suitable for use in thecompositions and methods of the present invention include, but are notlimited to: i) petroleum based oils (Group I, II and III), ii) syntheticoils (Group IV) and iii) biolubricant oils (vegetable oils such ascanola, soybean, corn oil etc.,). Group I oils, as defined herein aresolvent refined base oils. Group II oils, as defined herein are modernconventional base oils made by hydrocracking and early waxisomerization, or hydroisomerization technologies and have significantlylower levels of impurities than Group I oils. Group III oils, as definedherein are unconventional base oils. Groups I-III differ in impurities,and viscosity index as is shown in Kramer et al. “The Evolution of BaseOil Technology” Turbine Lubrication in the 21^(st) Century ASTM STP#1407 W. R. Herguth and T. M. Wayne, Eds., American Society for Testingand Materials, West Conshohocken, Pa., 2001 the entire contents of whichare incorporated herein by reference. Group IV oils as defined hereinare “synthetic” lubricant oils, including for example, poly-alphaolefins (PAOs). Biolubricants as defined herein are lubricants whichcontain at least 51% biomaterial (see Scott Fields, Environmental HealthPerspectives, volume 111, number 12, September 2003, the entire contentsof which are incorporated herein by reference). Other examples oflubricant oils cane be found in Melvyn F. Askew “Biolubricants-MarketData Sheet” IENICA, August 2004 (as part of the IENICA workstream of theIENICA-INFORRM project); Taylor et al. “Engine lubricant Trends Since1990” paper accepted for publication in the Proceedings I. Mech. E. PartJ, Journal of Engineering Tribology, 2005 (Vol. 219 p 1-16); andDesplanches et al. “Formulating Tomorrow's Lubricants” page 49-52 of ThePaths to Sustainable Development, part of special report published inOctober 2003 by Total; the entire contents of each of which areincorporated herein by reference. Biolubricants are often but notnecessarily, based on vegetable oils. Vegetable derived, for example,from rapeseed, sunflower, palm and coconut can be used as biolubricants.They can also be synthetic esters which may be partly derived fromrenewable resources. They can be made from a wider variety of naturalsources including solid fats and low grade or waste materials such astallows. Biolubricants in general offer rapid biodegradability and lowenvironmental toxicity.

As used herein, Group I, II and III oils are petroleum base stock oil.The petroleum industry differentiates their oil based on viscosity indexand groups them as Group I, II and III.

In certain embodiments of the present invention, 50% to 20% by weight ofthe antioxidants of the present invention are added to lubricant oils.In certain other embodiments of the present invention, 10% to 5% byweight of the antioxidants of the present invention are added tolubricant oils. In certain other embodiments of the present invention,0.1% to 2% by weight of the antioxidants of the present invention areadded to lubricant oils. In certain other embodiments of the presentinvention, 0.001% to 0.5% by weight of the antioxidants of the presentinvention are added to lubricant oils. This percentage varies dependingupon their end application and type of the base oil.

In certain embodiments of the present invention the antioxidants of thepresent invention are usually added to lubricant oils with stirring atbetween 0 and 100° C., between 20 and 80° C. or between 40-60° C.

The macromolecules of the present invention can also be made byalkylation of substituted amines, most preferably,N-phenyl-1,4-phenylene-diamine (II) in a suitable solvent by benzylhalides, e.g., preferably 3,5-di-tert-butyl-4-hydroxy benzyl chloride(IV) or 3,5-di-tert-butyl-4-hydroxy benzyl bromide (V) as shown inScheme 2.

EXEMPLIFICATION Example 1 Illustration of One Pot Process of MakingMacromolecules of the Present Invention in Large Scale

2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol (26.3 g) andN-Phenyl-1,4-phenylene-diamine (18.4 g) were dissolved in 50 ml toluene.The reaction mixture was refluxed at 100° C. using a Dean Starkapparatus equipped with a condenser. After completion, the solvent wasremoved by distillation and ice-cold water added and refluxed. Thereaction mixture was cooled to room temperature and product was isolatedby filtration. The product (A) was characterized using spectroscopictechniques such as high resolution ¹H NMR, ¹³C NMR and FT-IR.

Example 2 Performance of Macromolecules of the Present Invention inLubricating Oils

Macromolecule A was mixed with oil at 60° C. for 5-15 minutes at 200 ppmin petroleum based group II base stock oil and polyol based Group V basestock oils. It was tested using differential scanning calorimetry (DSC).Its Oxidative Induction Time (OIT) was also compared with commerciallyused antioxidants 2,6-di-tert-butyl-phenol, Naugalube APAN (PANA) andVanlube 81 (DODP). FIG. 1 shows the macromolecule A is superior inprotecting lubricating oils against oxidation.

Example 3 One Pot Process of Making Compound Having Structure I

2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol (3 g) andN-Phenyl-1,4-phenylene-diamine (2 g) were dissolved in 100 ml toluene.The reaction mixture was refluxed at 100° C. using a Dean's Starkapparatus equipped with a condenser. The reaction was monitored by thinlayer chromatography. After completion, the solvent was removed bydistillation and the resultant mixture was purified by columnchromatography. The purified compound was characterized by spectroscopictechniques.

Example 4 One Pot Process of Making Compound Having Structure II

2,6-di-tert-butyl-4-(dimethyl-aminomethyl)phenol (32 g) andN-Phenyl-1,4-phenylene-diamine (18.4 g) were dissolved in 50 ml toluene.The reaction mixture was refluxed at 100° C. using a Dean's Starkapparatus equipped with a condenser. After completion, the solvent wasremoved by distillation and ice-cold water added and refluxed. Thereaction mixture was cooled to room temperature and product was isolatedby filtration. The purified compound was characterized by spectroscopictechniques.

Example 5 One Pot Process of Making Structure V

2,6-di-tert-butyl phenol (10.3 g), paraformaldehyde (1.8 g) andN-hexyl-Phenyl-1,4-phenylene-diamine (16.08 g) were dissolved in 75 mlmethanol. The reaction mixture was refluxed at 70° C. using a Dean'sStark apparatus equipped with a condenser. After completion, the solventwas removed by distillation and ice-cold water added and refluxed. Thereaction mixture was cooled to room temperature and product was isolatedby filtration. The purified compound was characterized by spectroscopictechniques.

Example 6 One Pot Process of Making Structure X at

2-methyl,6-tert-butyl phenol (16.4 g), paraformaldehyde (3.6 g) andN-Phenyl-1,4-phenylene-diamine (22 g) were dissolved in 50 ml methanol.The reaction mixture was refluxed at 70° C. using a Dean's Starkapparatus equipped with a condenser. After completion, the solvent wasremoved by distillation and ice-cold water added and refluxed. Thereaction mixture was cooled to room temperature and product was isolatedby filtration and purified by column chromatography. The purifiedcompound was characterized by spectroscopic techniques.

Example 7 One Pot Process of Making Structure XVIII

2,4-di-tert-butyl phenol (20.6 g), paraformaldehyde (3.6 g) andN-Phenyl-1,4-phenylene-diamine (22 g) were dissolved in 50 ml methanol.The reaction mixture was refluxed at 70° C. using a Dean's Starkapparatus equipped with a condenser. After completion, the solvent wasremoved by distillation and ice-cold water added and refluxed. Thereaction mixture was cooled to room temperature and product was isolatedby filtration. The purified compound was characterized by spectroscopictechniques.

Example 8 Performance of Macromolecules of the Present Invention inLubricating Oils

Macromolecules V and A were tested for their performance in lubricantoils and polymers. The macromolecules were mixed in oil with stirring at60° C. for 5-15 mins at 200 ppm in petroleum based Group II base stockand polyol based Group V base stock oils. The performance of theseantioxidants were evaluated in lubricant base oil stocks including GroupII using the DSC technique for determining their oxidation inductiontimes measured in minutes (OIT) at 200° C. The OITs of the antioxidantshaving structures V and A were compared with commercial antioxidants[L57: Ciba's Irganox L57, 6PPD: N-hexyl phenyl-1,4-phenylene diamine CAS#793-24-8)]. The results are shown in FIG. 2 which shows the superiorperformance of V and A.

Macromolecule I, II, X and VIII are mixed in oil with stirring at 60° C.for 5-15 mins at 200 ppm in petroleum based Group II base stock andpolyol based Group V base stock oils. The performance of theseantioxidants is evaluated in lubricant base oil stocks including GroupII using the DSC technique for determining their oxidation inductiontimes measured in minutes (OIT) at 200° C. The OITs of these novelantioxidants having structures I, II, X, XVIII is compared withcommercial antioxidants [L57: Ciba's Irganox L57, dioctylated diphenylamine (DODP, CAS#68411-46-1); 6PPD: N-hexyl phenyl-1,4-phenylene diamineCAS #793-24-8)].

The summary of performance of antioxidants I, II, V, X, XVIII and A andtheir comparison with commercial antioxidants L 57 and 6PPD in syntheticpolyol ester based oil is shown in Table 1. The macromolecules weremixed in oil with stirring at 60° C. for 5-15 mins at 200 ppm inpetroleum based Group II base stock and polyol based Group V base stockoils. Table 1, shows the superior performance of these compounds.

TABLE 1 OIT values of various antioxidants in polyester based basestock. OIT @ 200 ppm Antioxidant (min) L 57 3 6PPD 22 V 36 A 37 II 32 I115 X 28 XVIII 25 # OIT values were measured by DSC at 200° C. havingOxygen at 20 ml/min

The performance of antioxidants I, II, V, X, XVIII and A were alsoevaluated in polyolefins especially in polypropylene (PP) and arecompared with the performance of commercially used antioxidant, Irganox1010 (from Ciba, CAS #6683-19-8). FIG. 3 shows the heat flow as afunction time for extruded PP samples containing antioxidants at 1000ppm level. These samples were prepared under identical processingconditions using a single screw extruder. oxidative induction time (OIT)was determined using ASTM D 3895-95, “Oxidative-Induction Time ofPolyolefins by Differential Scanning Calorimetry”.

Example 9 Increase Solubility of the Antioxidant V of the PresentInvention in Group II Base Stock

10 g of the antioxidant V was added to 90 g of Group II lubricant oilbase stock in a beaker. The resultant mixture was stirred for 15 mins ina oil bath maintained at 60° C. to give a homogenous solution. Thishomogenous solution was used for evaluation. This solubility is muchhigher than the typical industry standards of 1-2%.

The entire contents of each of the following are incorporated herein byreference.

-   Docket No.: 3805.1000-000; Provisional Patent Application No.    60/632,893, filed Dec. 3, 2004, Title: Process For The Synthesis Of    Polyalkylphenol Antioxidants, by Suizhou Yang, et al;-   Docket No.: 3805.1000-003; patent application Ser. No. 11/292,813    filed Dec. 2, 2005, Title: Process For The Synthesis Of    Polyalkylphenol Antioxidants, by Suizhou Yang, et al;-   Docket No.: 3805.1001-000; Provisional Patent Application No.    60/633,197, filed Dec. 3, 2004, Title: Synthesis Of Sterically    Hindered Phenol Based Macromolecular Antioxidants, by Ashish Dhawan,    et al.;-   Docket No.: 3805.1001-003; patent application Ser. No. 11/293,050;    filed Dec. 2, 2005, Title: Synthesis Of Sterically Hindered Phenol    Based Macromolecular Antioxidants, by Ashish Dhawan, et al.;-   Docket No.: 3805.1002-000; Provisional Patent Application No.    60/633,252, filed Dec. 3, 2004, Title: One Pot Process For Making    Polymeric Antioxidants, by Vijayendra Kumar, et al.;-   Docket No.: 3805.1002-003; patent application Ser. No. 11/293,049;    filed Dec. 2, 2005, Title: One Pot Process For Making Polymeric    Antioxidants, by Vijayendra Kumar, et al.;-   Docket No.: 3805.1003-000; Provisional Patent Application No.    60/633,196, filed Dec. 3, 2004, Title: Synthesis Of Aniline And    Phenol-Based Macromonomers And Corresponding Polymers, by Rajesh    Kumar, et al.;-   Docket No.: 3805.1003-003; patent application Ser. No. 11/293,844;    filed Dec. 2, 2005, Title: Synthesis Of Aniline And Phenol-Based    Macromonomers And Corresponding Polymers, by Rajesh Kumar, et al.;-   Docket No.: 3805.1004-002; patent application Ser. No. 11/184,724,    filed Jul. 19, 2005, Title: Anti-Oxidant Macromonomers And Polymers    And Methods Of Making And Using The Same, by Ashok L. Cholli;-   Docket No.: 3805.1004-005; patent application Ser. No. 11/184,716,    filed Jul. 19, 2005, Title: Anti-Oxidant Macromonomers And Polymers    And Methods Of Making And Using The Same, by Ashok L. Cholli;-   Docket No.: 3805.1005-000; Provisional Patent Application No.    60/655,169, filed Feb. 22, 2005, Title: Nitrogen And Hindered Phenol    Containing Dual Functional Macromolecules Synthesis And Their    Antioxidant Performances In Organic Materials, by Rajesh Kumar, et    al.-   Docket No.: 3805.1006-000; Provisional Patent Application No.    60/655,169, filed Mar. 25, 2005, Title: Alkylated Macromolecular    Antioxidants And Methods Of Making, And Using The Same, by Rajesh    Kumar, et al.-   Docket No.: 3805.1007-000; Provisional Patent Application No.    60/731,125, filed Oct. 27, 2005, Title: Macromolecular Antioxidants    And Polymeric Macromolecular Antioxidants, by Ashok L. Cholli, et    al.-   Docket No.: 3805.1008-000; Provisional Patent Application No.    60/731,021, filed Oct. 27, 2005, Title: Macromolecular Antioxidants    Based On Sterically Hindered Phenols And Phosphites, by Ashok L.    Cholli, et al.-   Docket No.: 3805.1009-000; Provisional patent application Ser. No.    ______, filed Dec. 2, 2005, Title: Lubricant Composition, by Kumar,    Rajesh, et al.-   Docket No.: 3805.1010-000; Provisional Patent Application No.    60/731,325, filed Oct. 27, 2005, Title: Stabilized. Polyolefin    Composition, by Kumar, Rajesh, et al.-   Docket No.: 0813.2006-003; patent application Ser. No. 11/040,193,    filed Jan. 21, 2005, Title: Post-Coupling Synthetic Approach For    Polymeric Antioxidants, by Ashok L. Cholli, et al.;-   Docket No.: 0813.2006-002; Patent Application No.:    PCT/US2005/001948, filed Jan. 21, 2005, Title: Post-Coupling    Synthetic Approach For Polymeric Antioxidants, by Ashok L. Cholli et    al.;-   Docket No.: 0813.2002-008; Patent Application No.:    PCT/US2005/001946, filed Jan. 21, 2005, Title: Polymeric    Antioxidants, by Ashok L. Cholli, et al.;-   Docket No.: 0813.2002-006; Patent Application No.: PCT/US03/10782,    filed Apr. 4, 2003, Title: Polymeric Antioxidants, by Ashok L.    Cholli, et al.;-   Docket No.: 0813.2002-004; patent application Ser. No. 10/761,933,    filed Jan. 21, 2004, Title: Polymeric Antioxidants, by Ashish    Dhawan, et al.;-   Docket No.: 0813.2002-001; patent application Ser. No. 10/408,679,    filed Apr. 4, 2003, Title: Polymeric Antioxidants, by Ashok L.    Cholli, et al.;-   U.S. Pat. No. 6,770,785 B1-   U.S. Pat. No. 5,834,544-   Neftekhimiya (1981), 21(2): 287-298.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the invention.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to specificembodiments of the invention described specifically herein. Suchequivalents are intended to be encompassed in the scope of the followingclaims.

1. A method of producing a compound represented by the followingstructural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R_(c)is independently an optionally substituted alkyl or an optionallysubstituted alkoxycarbonyl; R_(x) is —H or an optionally substitutedalkyl; R_(y) is —H or an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; R″ is —H, anoptionally substituted alkyl, an optionally substituted aryl or anoptionally substituted aralkyl; n is an integer from 1 to 10; m is aninteger from 1 to 10; s is an integer from 0 to 5; t is an integer from0 to 4; and u is an integer from 1 to 4; comprising: a) combining aphenol derivative, an amine and an aldehyde in the presence of asolvent, wherein the phenol derivative comprises at least oneunsubstituted ring-carbon atom; b) refluxing the combination of step a)to produce the compound; and c) isolating the compound.
 2. The method ofclaim 1, wherein the phenol derivative is represented by the followingstructural formula:

wherein: each R_(c) is independently an optionally substituted alkyl oralkoxycarbonyl; R′ is —H or an optionally substituted alkyl; and u is aninteger from 1 to
 4. 3. The method of claim 2, wherein the amine isrepresented by the following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; n is an integerfrom 1 to 10; s is an integer from 0 to 5; and t is an integer from 0 to4.
 4. The method of claim 3, wherein the aldehyde is selected from thegroup consisting of paraformaldehyde, formaldehyde, butaldehyde andnonaldehyde.
 5. The method of claim 4, wherein the solvent is selectedfrom the group consisting of methanol, butanol, ethanol and toluene. 6.The method of claim 5, wherein the combination is refluxed in step b)for between 12 and 24 hours with stirring.
 7. A method of producing acompound represented by the following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R_(c)is independently an optionally substituted alkyl or an optionallysubstituted alkoxycarbonyl; R_(x) is —H or an optionally substitutedalkyl; R_(y) is —H or an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; R″ is —H, anoptionally substituted alkyl, an optionally substituted aryl or anoptionally substituted aralkyl; n is an integer from 1 to 10; m is aninteger from 1 to 10; s is an integer from 0 to 5; t is an integer from0 to 4; and u is an integer from 1 to 4; comprising: a) combining aamino-phenol derivative with an amine in the presence of a solvent; b)refluxing the combination of step a) to produce the compound; and c)isolating the compound.
 8. The method of claim 7, wherein theamino-phenol derivative is represented by the following structuralformula:

wherein: each R_(c) is independently an optionally substituted alkyl oralkoxycarbonyl; R′ is —H or an optionally substituted alkyl; each R** isindependently an optionally substituted alkyl; o is an integer from 1 to10; and u is an integer from 1 to
 4. 9. The method of claim 8, whereinthe amine is represented by the following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; n is an integerfrom 1 to 10; s is an integer from 0 to 5; and t is an integer from 0 to4.
 10. The method of claim 9, wherein the solvent is selected from thegroup consisting of toluene, methanol, ethanol and butanol.
 11. Themethod of claim 10, wherein the combination is refluxed at a temperaturebetween 50 and 180° C. in step b).
 12. The method of claim 11, whereinthe combination is refluxed at a temperature between 90 and 130° C. instep b).
 13. The method of claim 12, wherein equimolar amounts of theamino-phenol derivative and the amine are combined in step a).
 14. Amethod of producing a compound represented by the following structuralformula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R_(c)is independently an optionally substituted alkyl or an optionallysubstituted alkoxycarbonyl; R_(x) is —H or an optionally substitutedalkyl; R_(y) is —H or an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; R″ is —H, anoptionally substituted alkyl, an optionally substituted aryl or anoptionally substituted aralkyl; R* is —H or an optionally substitutedalkyl; n is an integer from 1 to 10; m is an integer from 1 to 10; o isan integer from 0 to 10; s is an integer from 0 to 5; t is an integerfrom 0 to 4; and u is an integer from 1 to 4; comprising: a) combining aphenolic-carbonyl derivative represented by the following structuralformula:

with an amine in the presence of a solvent; b) refluxing the combinationof step a) to produce a schiff's base; c) reducing the schiff's basewith a reducing agent to produce the compound; and d) isolating thecompound.
 15. The method of claim 14, wherein the amine is representedby the following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; s is an integerfrom 0 to 5; t is an integer from 0 to 4; and n is an integer from 1 to10.
 16. The method of claim 15, wherein the solvent is selected from thegroup consisting of toluene, methanol, ethanol and butanol.
 17. Themethod of claim 16, wherein the combination is refluxed at a temperaturebetween 50 and 180° C. in step b).
 18. The method of claim 17, whereinthe combination is refluxed at a temperature between 90 and 130° C. instep b).
 19. The method of claim 18, wherein equimolar amounts of thephenolic-carbonyl derivative and the amine are combined in step a). 20.The method of claim 19, wherein the reducing agent is selected from thegroup consisting of sodium borohydride, lithium borohydride and sodiumcyanoborohydride.
 21. A method of producing a compound represented bythe following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R_(c)is independently an optionally substituted alkyl or an optionallysubstituted alkoxycarbonyl; R_(x) is —H or an optionally substitutedalkyl; R_(y) is —H or an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; R″ is —H, anoptionally substituted alkyl, an optionally substituted aryl or anoptionally substituted aralkyl; n is an integer from 1 to 10; m is aninteger from 1 to 10; s is an integer from 0 to 5; t is an integer from0 to 4; and u is an integer from 1 to 4; comprising: a) combining aformaldehyde-sodium bisulfite adduct with an amine in aqueous media toproduce a methylsulfonate sodium salt; b) displacing the sulfonate groupof the methylsulfonate sodium salt via nucleophilic displacement with asodium or potassium salt of a phenol derivative, in an aqueous media,wherein the nucleophilic displacement is catalyzed base to produce thecompound; and b) isolating the compound.
 22. The method of claim 21,wherein the phenol derivative is represented by the following structuralformula:

wherein: each R_(c) is independently an optionally substituted alkyl oralkoxycarbonyl; R′ is —H or an optionally substituted alkyl; and u is aninteger from 1 to
 4. 23. The method of claim 22, wherein the amine isrepresented by the following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; n is an integerfrom 1 to 10; s is an integer from 0 to 5; and t is an integer from 0 to4.
 24. The method of claim 23, wherein the aqueous media is water. 25.The method of claim 24, wherein the formaldehyde-sodium bisulfate adductis is HO—CH₂—SO₃Na.
 26. The method of claim 25, wherein the base issodium hydroxide or potassium hydroxide.
 27. The method of claim 26,wherein the methylsulfonate sodium salt is 4-(phenylamino)phenylaminomethylsulfonate sodium salt.
 28. A method of preventing oxidation in anoxidizable material, comprising combining the oxidizable material with acompound represented by the following structural formula:

wherein: each R_(a) is independently an optionally substituted alkyl;each R_(b) is independently an optionally substituted alkyl; each R_(c)is independently an optionally substituted alkyl or an optionallysubstituted alkoxycarbonyl; R_(x) is —H or an optionally substitutedalkyl; R_(y) is —H or an optionally substituted alkyl; each R′ isindependently —H or an optionally substituted alkyl; R″ is —H, anoptionally substituted alkyl, an optionally substituted aryl or anoptionally substituted aralkyl; n is an integer from 1 to 10; m is aninteger from 1 to 10; is an integer from 0 to 5; t is an integer from 0to 4; and u is an integer from 1 to
 4. 29. The method of claim 1,wherein the compound is represented by the following structural formula:

wherein R′=

or a substituted alkyl; wherein n=1-3; wherein the phenol derivative is:

wherein the amine is:

and wherein the aldehyde is formaldehyde.
 30. The method of claim 14,wherein the compound is represented by the following structural formula:

wherein R′=

or a substituted alkyl; and wherein n=1-3.
 31. The method of claim 21,wherein the compound is represented by the following structural formula:

wherein R′=

or a substituted alkyl; and wherein n=1-3.
 32. The method of claim 28,wherein the oxidizable material is combined with a compound isrepresented by the following structural formula:

wherein R′=

or a substituted alkyl; and wherein n=1-3.